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dc.contributor.authorRappazzo, C Garrett
dc.contributor.authorHsieh, Ching-Lin
dc.contributor.authorRush, Scott A
dc.contributor.authorEsterman, Emma S
dc.contributor.authorDelgado-Romero, Teresa 
dc.contributor.authorGeoghegan, James C
dc.contributor.authorWec, Anna Z
dc.contributor.authorSakharkar, Mrunal
dc.contributor.authorMas-Lloret, Vicente 
dc.contributor.authorMcLellan, Jason S
dc.contributor.authorWalker, Laura M
dc.date.accessioned2023-05-09T11:58:29Z
dc.date.available2023-05-09T11:58:29Z
dc.date.issued2022-09-13
dc.identifier.citationImmunity. 2022 Sep 13;55(9):1710-1724.e8.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/16032
dc.description.abstractHuman metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens.es_ES
dc.description.sponsorshipWe acknowledge the Immune Monitoring and Flow Cytometry Resource (IMFCSR) at the Norris Cotton Cancer Center at Dartmouth supported by NCI Cancer Center Support Grant 5P30CA023108-41. This work was funded in part by Welch Foundation grant number F-0003-19620604.es_ES
dc.language.isoenges_ES
dc.publisherElsevier es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshAntibodies, Neutralizing es_ES
dc.subject.meshAntibodies, Viral es_ES
dc.subject.meshMetapneumovirus es_ES
dc.subject.meshRespiratory Tract Infections es_ES
dc.subject.meshAged es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshEpitopes es_ES
dc.subject.meshGlycoproteins es_ES
dc.subject.meshHumans es_ES
dc.subject.meshViral Fusion Proteins es_ES
dc.subject.meshYoung Adult es_ES
dc.titlePotently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoproteines_ES
dc.typejournal articlees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID35944529es_ES
dc.format.volume55es_ES
dc.format.number9es_ES
dc.format.page1710-1724.e8es_ES
dc.identifier.doi10.1016/j.immuni.2022.07.003es_ES
dc.contributor.funderNIH - National Cancer Institute (NCI) (Estados Unidos) es_ES
dc.contributor.funderWelch Foundation es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1097-4180es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.immuni.2022.07.003es_ES
dc.identifier.journalImmunityes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 Internacional